Apatinib plus paclitaxel versus paclitaxel monotherapy for platinum‐resistant recurrent ovarian cancer treatment: A retrospective cohort study

alexandrossfakianakis shared this article with you from Inoreader Apatinib plus paclitaxel versus paclitaxel monotherapy for platinum‐resistant recurrent ovarian cancer treatment: A retrospective cohort study via Journal of Clinical Pharmacy and Therapeutics This retrospective cohort study reviewed 70 platinum-resistant recurrent ovarian cancer (PROC) patients who received apatinib plus paclitaxel (apatinib plus paclitaxel group) (N = 32) or paclitaxel monotherapy (paclitaxel monotherapy group) (N = 38). The recommended regimens were as follows: paclitaxel (60 mg/m2) administrated once a week with a maximum of 18 weeks; apatinib (250–375 mg/day) administrated until disease progression or patient intolerance. Interestingly, disease control rate was elevated (84.4% vs. 60.5%, P = 0.028), whereas objective response rate only disclosed an increasing trend (lacked statistical significance) (37.5% vs. 18.4%, P = 0.074) in apatinib plus paclitaxel group compared with paclitaxel monotherapy group. Progression-free survival (median [95% CI]: 5.0 [2.5–7.5] months vs. 3.8 [2.4–5.2] months, P = 0.033) and overall survival (median [95% CI]: 21.1 [13.2–29.0] months vs. 14.8 [11.4–18.2] months, P = 0.032) were both prolonged in apatinib plus paclitaxel group compared to paclitaxel monotherapy group, which were further verified in the multivariate Cox's proportional hazard regression analyses (both P < 0.050). Additionally, the incidence of each adverse event was not different between the two groups (all P > 0.050). Collectively, apatinib plus paclitaxel exhibits better efficacy and acceptable toxicity compared with paclitaxel monotherapy in PROC patients. Abstract What Is Known and Objective Apatinib, an oral antiangiogenic drug, exerts potential anti-tumour effects on platinum-resistant recurrent ovarian cancer (PROC). This study intended to evaluate the efficacy and safety of apatinib plus paclitaxel compared to paclitaxel monotherapy in PROC patients. Methods This retrospective cohort study reviewed 70 PROC patients who received apatinib plus paclitaxel (apatinib plus paclitaxel group) (N = 32) or paclitaxel monotherapy (paclitaxel monotherapy group) (N = 38). The recommended regimens were as follows: paclitaxel (60 mg/m2) administrated once a week with a maximum of 18 weeks; apatinib (250–375 mg/day) administrated until disease progression or patient intolerance. Results and Discussion Disease control rate was elevated (84.4% vs. 60.5%, P = 0.028), whereas objective response rate only disclosed an increasing trend (lacked statistical significance) (37.5% vs. 18.4%, P = 0.074) in apatinib plus paclitaxel group compared with paclitaxel monotherapy group. Progression-free survival (median [95% confidence interval (CI)]: 5.0 [2.5–7.5] months vs. 3.8 [2.4–5.2] months, P = 0.033) and overall survival (median [95% CI]: 21.1 [13.2–29.0] months vs. 14.8 [11.4–18.2] months, P = 0.032) were both prolonged in apatinib plus paclitaxel group compared to paclitaxel monotherapy group, which were further verified in the multivariate Cox's proportional hazard regression analyses (both P < 0.050). Additionally, the incidence of each adverse event was not different between the two groups (all P > 0.050). What is New and Conclusion Apatinib plus paclitaxel exhibits better efficacy and acceptable toxicity compared with paclitaxel monotherapy in PROC patients. View on Web

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A Dual‐targeting Near‐infrared Biomimetic Drug Delivery System for HBV Treatment

alexandrossfakianakis shared this article with you from Inoreader A Dual‐targeting Near‐infrared Biomimetic Drug Delivery System for HBV Treatment via Journal of Medical Virology Abstract Hepatitis B virus (HBV) infection is a serious global public health threat. It remains elusive to achieve a functional HBV cure with currently available antivirals. Herein, a photo-responsive delivery vehicle composed of Nd3+-sensitized core-shell upconversion nanoparticle (UCNP), mesoporous silica nanoparticle (MSN), antisense oligonucleotides (ASO), and capsid-binding inhibitor C39 was established, which was named UMAC according to the initials of its components. Subsequently, the as-synthesized delivery vehicle was encapsulated by β-D-galactopyranoside (Gal) modified red blood cell (RBC) membrane vesicles, which enabled precise targeting of the liver cells (UMAC-M-Gal). Both in vitro and in vivo experiments demonstrated that this biomimetic system could successfully achieve controlled drug release under light conditions at 808 nm, leading to effective suppression of HBV replication in this dual-targeted therapeutic approach. Together, these results sub stantiate the system has huge prospects for application to achieve functional HBV cure, and provides a promising novel strategy for drug delivery. This article is protected by copyright. All rights reserved. View on Web

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AZD7442 (Tixagevimab/Cilgavimab) for Post-exposure Prophylaxis of Symptomatic COVID-19

alexandrossfakianakis shared this article with you from Inoreader AZD7442 (Tixagevimab/Cilgavimab) for Post-exposure Prophylaxis of Symptomatic COVID-19 via Clinical Infectious Diseases Advance Access Abstract Background We report primary results of a phase 3 trial of AZD7442 (tixagevimab/cilgavimab) for post-exposure prophylaxis to prevent symptomatic coronavirus disease 2019 (COVID-19) Methods Adults without prior SARS-CoV-2 infection or COVID-19 vaccination were enrolled within 8 days of exposure to a SARS-CoV-2–infected individual and randomized 2:1 to a single 300-mg AZD7442 dose (one 1.5-mL intramuscular injection each of tixagevimab and cilgavimab consecutively) or placebo. Primary endpoints were safety and first post-dose SARS-CoV-2 reverse-transcription–polymerase-chain-reaction (RT-PCR)–positive symptomatic COVID-19 event before day 183. Results 1121 participants were randomized and dosed (mean age 46 years; 49% females; AZD7442, n=749; placebo, n=372). Median (range) follow-up was 49 (5–115) and 48 (20–113) days for AZD7442 and placebo, respectively. Adverse events occurred in 162/749 (21.6%) and 111/372 (29.8%) participants with AZD7442 and placebo, respectively, mostly mild/moderate. RT-PCR–positive symptomatic COVID-19 occurred in 23/749 (3.1%) and 17/372 (4.6%) AZD7442- and placebo-treated participants, respectively (relative risk reduction 33.3%; 95% confidence interval [CI] –25.9 to 64.7; P=.21). In predefined subgroup analyses of 1073 (96%) participants who were SARS-CoV-2 RT-PCR–negative (n=974 [87%]) or missing an RT-PCR result (n=99 [9%]) at baseline, AZD7442 reduced RT-PCR–positive symptomatic COVID-19 by 73.2% (95% CI 27.1 to 90.1) versus placebo. Conclusions This study did not meet the primary efficacy endpoint of post-exposure prevention of symptomatic COVID-19 with AZD7442 versus placebo. However, predefined analysis of participants who were SARS-CoV-2 RT-PCR–negative or missing an RT-PCR result at baseline support a role for AZD7442 in preventing symptomatic COVID-19. View on Web

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Inverted repeats in the monkeypox virus genome are hot spots for mutation

alexandrossfakianakis shared this article with you from Inoreader Inverted repeats in the monkeypox virus genome are hot spots for mutation via Journal of Medical Virology Abstract The current monkeypox virus (MPXV) strain differs from the strain arising in 2018 by 50+ single nucleotide polymorphisms (SNPs) and is mutating much faster than expected. The cytidine deaminase apolipoprotein B mRNA editing enzyme, catalytic subunit B (APOBEC3) was hypothesised to be driving this increased mutation. APOBEC has recently been identified to preferentially mutate cruciform DNA secondary structures formed by inverted repeats (IRs). IRs were recently identified as hot spots for mutation in SARS-CoV-2, and we aimed to identify whether IRs were also hot spots for mutation within MPXV genomes. We found that MPXV genomes were replete with IR sequences. Of the 50+ SNPs identified in the 2022 outbreak strain, 63.9% of these were found to have arisen within IR regions in the 2018 reference strain (MT903344.1). Notably, IR sequences found in the 2018 reference strain were significantly lost over time, with an average of 32.5% of these sequences being cons erved in the 2022 MPXV genomes. This evidence was highly indicative that mutations were arising within IRs. This data provides further support to the hypothesis that APOBEC may be driving MPXV mutation and highlights the necessity for greater surveillance of IRs of MPXV genomes to detect new mutations. This article is protected by copyright. All rights reserved. View on Web

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Infection phase‐dependent dynamics of the viral and host N6‐methyladenosine epitranscriptome in the lifecycle of an oncogenic virus in vivo

alexandrossfakianakis shared this article with you from Inoreader Infection phase‐dependent dynamics of the viral and host N6‐methyladenosine epitranscriptome in the lifecycle of an oncogenic virus in vivo via Journal of Medical Virology ABSTRACT Dynamic alteration of the epitranscriptome exerts regulatory effects on the lifecycle of oncogenic viruses in vitro. However, little is known about these effects in vivo because of the general lack of suitable animal infection models of these viruses. Using a model of rapid-onset Marek's disease lymphoma in chickens, we investigated changes in viral and host mRNA N6-methyladenosine (m6A) modification during Marek's disease virus (MDV) infection in vivo. We found that the expression of major epitranscriptomic proteins varies among viral infection phases, reprogramming both the viral and the host epitranscriptomes. Specifically, the METTL3/14 complex was suppressed during the lytic and reactivation phases of the MDV lifecycle, whereas its expression was increased during the latent phase and in MDV-induced tumors. METTL3/14 overexpression inhibits, whereas METTL3/14 knockdown enhances, MDV gene expression and replication. These f indings reveal the dynamic features of the mRNA m6A modification program during viral replication in vivo, especially in relation to key pathways involved in tumorigenesis. This article is protected by copyright. All rights reserved. View on Web

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The effect of SARS‐CoV‐2 infection on cardiac function in post‐COVID‐19 survivors: A systematic review and meta‐analysis

alexandrossfakianakis shared this article with you from Inoreader The effect of SARS‐CoV‐2 infection on cardiac function in post‐COVID‐19 survivors: A systematic review and meta‐analysis via Journal of Medical Virology Abstract Objective The longitudinal trajectories of cardiac structure and function following SARS-CoV-2 infection are unclear. Therefore, this meta-analysis aims to elucidate the effect of SARS-CoV-2 infection on cardiac function in COVID-19 survivors after recovery. Methods PubMed/MEDLINE, CENTRAL, and EMBASE were systematically searched for articles published up to 1st August 2022. A systematic review and meta-analysis were performed to calculate the pooled effects size and 95% confidence interval (CI) of each outcome. Results Twenty-one studies including 2394 individuals (1436 post-COVID-19 cases and 958 controls) were included in the present meta-analysis. The pooled analyses compared with control groups showed a significant association between post-COVID-19 and reduced left ventricular ejection fraction (LV EF), LV end-diastolic volume (LV EDV), LV stroke volume (LV SV), mitral annular plane systolic excursion (MAPSE), global longitudinal strain (GLS), right ventricular EF (RV EF), RV EDV, RV ESV, RV SV, tricuspid annular plane systolic excursion (TAPSE), and increased LV mass. Subgroup analysis based on the severity of COVID-19 in the acute phase and subsequent chronic outcomes revealed that LV EF, MAPSE, RV EF, and RV ESV only decreased in studies including patients with a history of intensive care unit (ICU) admission. Conclusion Cardiac impairment after SARS-CoV-2 infection persisted in recovered COVID-19 patients even after one year. Future studies are warranted to determine the biological mechanisms underlying the long-term cardiovascular consequences of COVID-19. This article is protected by copyright. All rights reserved. View on Web

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CTIM-22. THE COMBINATION OF LOMUSTINE AND THE IMMUNOCYTOKINE L19TNF IS A PROMISING TREATMENT FOR RECURRENT GLIOBLASTOMA

alexandrossfakianakis shared this article with you from Inoreader CTIM-22. THE COMBINATION OF LOMUSTINE AND THE IMMUNOCYTOKINE L19TNF IS A PROMISING TREATMENT FOR RECURRENT GLIOBLASTOMA via # Neuro-Oncology Current Issue Abstract Glioblastoma is the most aggressive primary brain tumor and adults and poorly immunogenic. Treatment options for recurrent glioblastoma after standard of care chemoradiation are limited Several immunotherapeutic strategies including peptide vaccination and immune checkpoint inhibition have so far failed to improve survival and except from potentially regorafenib, no other agent has demonstrated superior activity to lomustine. Therefore, there is an urgent need for more effective treatment strategies for recurrent glioblastoma. Here, we investigate a new treatment combination based on the alkylating chemotherapy lomustine and the tumor-stroma targeting antibody-cytokine fusion protein L19TNF in preclinical glioma models and patients with recurrent glioblastoma. The combination treatment with lomustine and L19TNF demonstrated strong synergistic anti-tumor activity in several immunocompetent orthotopic glioma models curing the majority of tumor-bear ing mice, whereas other mono- or combination therapies for example with anti-PD1 had only limited anti-glioma activity. Investigations of the mechanism of action revealed that lomustine plus L19TNF led to intratumoral necrosis, DNA damage and triggered a strong local anti-tumor immune response with increased MHC-I expression, presentation of neoepitopes and increased abundance of tumor-infiltrating lymphoid cells. In the first patients treated within a phase I/II clinical trial (NCT04573192), the treatment was well tolerated, and durable objective tumor responses and disease stabilizations could be observed also in patients with an unmethylated MGMT promoter. View on Web

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